Korn E L, Simon R
Biometric Research Branch, National Cancer Institute, Bethesda, MD 20892.
Breast Cancer Res Treat. 1992 Mar;20(3):155-66. doi: 10.1007/BF01834621.
A mathematical model previously described is applied to the problem of selecting drug combinations for metastatic breast cancer. The model accounts for the differing single-agent activities of the drugs as well as their differing profiles of toxicity. With no bone marrow protection, combinations with cisplatin offer a small improvement in total equivalent dose over therapy with the more active single-agents. Restricting consideration to the four most commonly used agents, single-agent doxorubicin has the greatest equivalent dose. With protection for leukopenia or willingness to accept a higher incidence of severe leukopenia, a combination with large doses of cyclophosphamide, doxorubicin, and fluorouracil, and a small dose of cisplatin has greatest equivalent dose. The doublets cyclophosphamide/fluorouracil or fluorouracil/cisplatin at higher doses are almost as good. With protection for leukopenia and thrombocytopenia, a cyclophosphamide/thiotepa combination at very high doses maximizes total equivalent dose. This approach can be used to identify regimens worthy of prospective evaluation.
一个先前描述的数学模型被应用于转移性乳腺癌药物组合选择的问题。该模型考虑了药物不同的单药活性以及它们不同的毒性特征。在没有骨髓保护的情况下，与顺铂联合用药相比使用更具活性的单药治疗，在总等效剂量上有小幅改善。若将考虑范围限制在四种最常用的药物，单药阿霉素的等效剂量最大。若对白细胞减少症进行保护或愿意接受更高的严重白细胞减少症发生率，大剂量环磷酰胺、阿霉素和氟尿嘧啶与小剂量顺铂的联合用药等效剂量最大。较高剂量的环磷酰胺/氟尿嘧啶或氟尿嘧啶/顺铂双联组合几乎同样有效。若对白细胞减少症和血小板减少症进行保护，极高剂量的环磷酰胺/噻替派联合用药可使总等效剂量最大化。这种方法可用于识别值得进行前瞻性评估的治疗方案。
